Abstract In this paper,we present amulti-scale optimizationmodel and an entropybased
genetic algorithm for molecular docking. In this model, we introduce to the
refined docking design a concept of residue groups based on induced-fit and adopt a
combination of conformations in different scales. A new iteration scheme, in conjunction
with multi-population evolution strategy, entropy-based searching technique with
narrowing down space and the quasi-exact penalty function, is developed to address the
optimization problem for molecular docking. A new docking program that accounts
for protein flexibility has also been developed. The docking results indicate that the
method can be efficiently employed in structure-based drug design.